We propose to utilize the cogenitally athymic (nude) mouse for investigations of three general areas of oncology. 1. The nude mouse will be used in studies designed to help define the role of the thymus gland in the development of spontaneous and chemically-induced tumors in mice. Our preliminary studies indicated that nude mice are refractory to chemical carcinogenesis. We will determine whether or not this is a general phenomenon, or limited to only certain carcinogens, by treating nudes with different carcinogens administered by various routes. The mechanism by which nudes are refractory to chemical carcinogenesis will be studied. Unoperated nudes and nude mice with thymus gland implants (and hence cell-mediated immunity) will be observed for the development of spontaneous and chemically-induced tumors to evaluate the role played by immunological surveillance and immunostimulation. Metabolites of carcinogenic agents and homografts of normal mouse skin on nude mice will be used to to determine if nude mice are refractory to carcinogens because of some as yet undetermined skin abnormality. 2. We seek to define the usefulness of nude mice for the in vivo propagation of tumor homografts and heterografts, including human tumors. In vivo studies of tumor growth, tumor immunity, hormonal effects and chemotherapeutic agents done using tumors propagated in nude mice will not be complicated by the use of immunosuppressive agents. 3. We have previously shown that nude mice will permanently accept heterografts of normal human skin. We seek to extend this observation to other normal human tissues. By treating such human heterografts on nude mice with chemical carcinogens, we hope to develop a model system for use in studies of the induction of neoplastic disorders in human tissues. Bibliographic references: Jacobson, R.H. and N.D. Reed. 1974. The thymus dependency of resistance to pinworm infection in mice. J. Parasitology 60:976-979. Jacobson, R.H. and N.D. Reed. 1974. The immune response of congenitally athymic (nude) mice to the intestinal nematode Nippostrongylus brasiliensis. Pro. Soc. Exp. Biol. Med. 147: 667-670.